Visceral leishmaniasis remains a disease of major health significance, and considerable research is required to understand the nature of intracellular parasitism exemplified by this desease. Of particular importance is the mode of entry of the parasites into the host cells and the specific receptors that mediate contact and adherence in the leishmania-phagocyte interaction. There is growing evidence that these receptors are glycoproteins, which can be identified and isolated through the use of lectins and other probes such as sugar-binding myeloma immunoblobulins. The goal of Project I is to identify, isolate and characterize these receptors as fully as possible and then determine their efficacy as vaccines to protect experimental hosts from challenge infections. Moreover, these antigens or others may be involved in pathogenesis, in particular, the immunological dysfunctions, such as hypergammaglobulinemia, that accompany the disease. The goal of Project II, therefore, is to determine whether polyclonal B cell activation occurs as a result of leishmanial mitogens, to examine autoimmunity, and to identify defects in T cell regulation. The basic information that will result from thse studies may be of value in prevention and therapy of the disease, and new classes of substances in lieshmania may be revealed that could be of value to fundamental studies in cell biology.